tretinoin and Keloid

Hypertrophic scars and keloids are common problems after injury and cause functional and cosmetic deformities. A wide variety of treatments have been advocated for hypertrophic scars and keloids regression. Unfortunately, the reported efficacy has been variable. This article explores antimitotic drugs described in the literature such as steroid injection, 5-FU, mitomycin C, and bleomycin, which mainly target the fibroblasts in scar tissue, have been proposed as the effective modalities for scar treatment and scar prevention after surgery, but restricted due to possible side effects. The current accepted treatment for hypertrophic scar and keloid are combination therapy and the early treatment which could achieve better efficacy and less adverse effect.

Topics: Antimetabolites, Antineoplastic; Apoptosis; Bleomycin; Cicatrix, Hypertrophic; Colchicine; Drug Therapy, Combination; Fibroblasts; Fluorouracil; Glucocorticoids; Humans; Injections, Intralesional; Keloid; Mitomycin; Mitosis Modulators; Treatment Outcome; Tretinoin; Triamcinolone

Scars are a common complication of surgery or burn wound management. Scars occur over the body, affecting people of both sexes and all ages. Scar therapy is a constant clinical challenge; antimitotic drugs and radiotherapy are used with varying degrees of success. This article examines the success of both these types of treatment modalities.

Topics: Adrenal Cortex Hormones; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antimitotic Agents; Cicatrix, Hypertrophic; Colchicine; Fluorouracil; Humans; Keloid; Keratolytic Agents; Mitomycin; Radiotherapy; Tretinoin; Tubulin Modulators

Topical vitamin A acid (VAA) has various mechanisms of action which may be responsible for its therapeutic success in many different disorders. Although the absorption, metabolism, and excretion of VAA are not completely understood, VAA appears to remain mainly on the skin surface. The question of carcinogenicity is unresolved, and more research is needed to clarify this problem. This article reviews the literature regarding the therapeutic uses of VAA and summarizes various investigators' experiences with VAA.

Topics: Acne Vulgaris; Animals; Callosities; Cocarcinogenesis; Fox-Fordyce Disease; Humans; Ichthyosis; Keloid; Keratoacanthoma; Keratosis; Lichen Planus; Melanoma; Melanosis; Molluscum Contagiosum; Nevus; Psoriasis; Skin Absorption; Skin Diseases; Skin Neoplasms; Tretinoin

Keloid disease is a recurrent fibroproliferative cutaneous tumor of unknown pathogenesis for which clinical management remains unsatisfactory. To obtain new insights into hitherto underappreciated aspects of keloid pathobiology, we took a laser capture microdissection-based, whole-genome microarray analysis approach to identify distinct keloid disease-associated gene expression patterns within defined keloid regions. Identification of the aldo-keto reductase enzyme AKR1B10 as highly up-regulated in keloid epidermis suggested that an imbalance of retinoic acid metabolism is likely associated with keloid disease. Here, we show that AKR1B10 transfection into normal human keratinocytes reproduced the abnormal retinoic acid pathway expression pattern we had identified in keloid epidermis. Cotransfection of AKR1B10 with a luciferase reporter plasmid showed reduced retinoic acid response element activity, supporting the hypothesis of retinoic acid synthesis deficiency in keloid epidermis. Paracrine signals released by AKR1B10-overexpressing keratinocytes into conditioned medium resulted in up-regulation of transforming growth factor-β1, transforming growth factor-β2, and collagens I and III in both keloid and normal skin fibroblasts, mimicking the typical profibrotic keloid profile. Our study results suggest that insufficient retinoic acid synthesis by keloid epidermal keratinocytes may contribute to the pathogenesis of keloid disease. We refocus attention on the role of injured epithelium in keloid disease and identify AKR1B10 as a potential new target in future management of keloid disease.

Topics: Aldehyde Reductase; Aldo-Keto Reductases; Culture Media, Conditioned; Epidermis; Fibroblasts; Fibrosis; Gene Expression Regulation; Humans; Keloid; Keratinocytes; Oligonucleotide Array Sequence Analysis; Plasmids; Response Elements; Signal Transduction; Transcriptional Activation; Tretinoin; Up-Regulation

Numerous modalities have been used to treat keloids and hypertrophic scars; however, optimal treatment has not yet been established. Therefore, prevention is the mainstay. Recently, silicone gel and tretinoin cream have been shown to be useful for the prevention of hypertrophic scars and keloids. However, there has been no comparative study of the two topical agents thus far.. To determine and compare the effectiveness of silicone gel and tretinoin cream for the prevention of hypertrophic scars and keloids resulting from postoperative wounds and for scar improvement.. This study included 26 patients with 44 different wounds. The postoperative wounds were divided into two treatment groups and one control group. The patients in the first and second treatment group applied silicone gel and tretinoin cream, respectively, twice a day on their wounds after their stitches were removed. In contrast, the control group patients did not apply anything. We used the Modified Vancouver Scar Scale to quantitatively examine the effectiveness of silicone gel and tretinoin cream just after stitches removal, and at 4, 8, 12 and 24 weeks after removal of the stitches.. The silicone gel and tretinoin cream effectively prevented hypertrophic scars and keloids and improved scar effects in the two treatment groups compared with those in the control group. However, no significant difference was noted between the two treatment groups.. To prevent hypertrophic scars and keloids and improve scars after surgery, application of a silicone gel or a tretinoin cream to the wounds is needed.

Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Child, Preschool; Cicatrix, Hypertrophic; Female; Humans; Keloid; Male; Middle Aged; Silicone Gels; Tretinoin; Young Adult

Keloids are skin abnormalities that are characterized by excessive deposition of collagen bundles in the dermis. Patients with keloids complain not only about their cosmetic appearance, but also about continuous itching and/or tenderness associated with chronic inflammation. Degradation of extracellular matrix (ECM) may be upregulated, associated with the expansion of keloids into circumferential skin, and high metabolic activity of keloid tissues may be due to increased matrix metalloproteinase (MMP) activity. Based on these hypotheses, we examined differences in expression of MMP-1, MMP-8, and MMP-13 between keloid-derived and normal dermal fibroblasts. Since retinoids are potent inhibitors of MMPs in the treatment of photoaged skin and cancers, we also examined whether or not tretinoin affects MMP expression of keloid-derived fibroblasts. The results of real-time polymerase chain reaction and ELISA demonstrated significant upregulation of MMP-13 and significant downregulation of MMP-1 and MMP-8 in keloid-derived fibroblasts, at both mRNA and protein levels. MMP-1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group. MMP-8 mRNA expression in the control group was significantly upregulated by tretinoin, with the peak at 12 h, while no significant change was observed in the keloid-derived fibroblasts. In contrast, the remarkably elevated MMP-13 mRNA expression in the keloid group was significantly suppressed, with the peak suppression at 12 h after addition of tretinoin, while MMP-13 mRNA expression in the control group was not significantly changed. The decrease in MMP-1 and MMP-8 may contribute to accumulation of type I and type III collagen in keloid tissues, and this mechanism may be modulated by molecular interaction with MMP-13. Tretinoin appeared to reverse the abnormal expression profile of MMPs in keloid-derived fibroblasts, such as markedly elevated expression of MMP-13, partly through inactivation of AP-1 pathway. The present results suggest that tretinoin may be clinically useful to improve the chronic inflammation seen in keloids and prevent expansion of keloid tissues into circumferential normal skin.

Topics: Adult; Collagenases; Culture Media; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Humans; Keloid; Keratolytic Agents; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 13; Matrix Metalloproteinase 8; Matrix Metalloproteinase Inhibitors; Middle Aged; Phosphoprotein Phosphatases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin; Tretinoin; Up-Regulation

Topics: Acne Vulgaris; Biopsy; Cell Division; Cells, Cultured; Collagen; Fibroblasts; Humans; Keloid; Procollagen; Skin; Tretinoin

We report the observation of delayed wound healing and keloid formation in three patients, following dermabrasion or Argon laser treatment administered while they were receiving isotretinoin for acne or rosacea.

Topics: Acne Vulgaris; Adult; Aged; Dermabrasion; Female; Humans; Isomerism; Isotretinoin; Keloid; Laser Therapy; Male; Rosacea; Tretinoin; Wound Healing

Since retinoids affect collagen metabolism, nine females and two males with keloids were treated with 0.05% tretinoin topically for 12 weeks. The lesions had been present for an average of 7 years prior to therapy. Changes in size were evaluated by serial kodachromes, tape measurements, and appreciation of volume using dental moulages. Two patients abandoned the study due to irritant contact dermatitis. A significant decrease in weight (p less than 0.04) and size (p less than 0.01) was found when comparing the status of the lesions at the beginning of the study and at week 12.

Topics: Administration, Topical; Drug Administration Schedule; Female; Humans; Keloid; Male; Tretinoin

In the present study, we have determined the specific glucocorticoid receptors in cultured human skin fibroblasts with [3H]dexamethasone as the ligand. The whole-cell assay was employed for determination of glucocorticoid receptor densities and binding affinities in fibroblast cultures established either from 16 healthy control subjects, from 4 patients with active progressive systemic sclerosis (PSS), from 3 patients with keloids and 3 patients with diabetes mellitus. The receptor densities in PSS, keloid, diabetes and control fibroblasts were in the same range, the values being 6.3 +/- 4.9, 7.7 +/- 3.6, 5.3 +/- 1.3 and 7.9 +/- 6.2 fmol/micrograms DNA (mean +/- SD), respectively. In further studies, the cells were incubated with 10(-7) M dexamethasone for 4 or 9 days before the receptors were assayed. The specific binding of [3H]dexamethasone in steroid treated cultures was 62 and 13% of that observed in controls, suggesting down-regulation. In contrast, incubation of fibroblasts with 10(-5) M all-trans-retinoic acid did not alter the binding of [3H]dexamethasone, suggesting lack of pharmacologic interference at the receptor level.

Topics: Cells, Cultured; Dexamethasone; Diabetes Mellitus; Fibroblasts; Humans; In Vitro Techniques; Keloid; Receptors, Glucocorticoid; Scleroderma, Systemic; Skin; Tretinoin

Six patients underwent dermabrasion while on or having recently completed isotretinoin (Accutane) therapy. All patients developed keloids in atypical locations; the keloids eventually responded to topical or intralesional steroid therapy. Retinoids have a modulatory effect on connective tissue metabolism, including suppression of collagenase, which may enhance keloid formation. Dermabrasion should be delayed in those patients taking or recently on isotretinoin therapy.

Topics: Acne Vulgaris; Adult; Dermabrasion; Female; Humans; Isotretinoin; Keloid; Male; Microbial Collagenase; Middle Aged; Tretinoin

There are relatively few studies of the effect of retinoids on dermal tissue. A selective review of the literature reveals that when retinoids, especially all-trans-retinoic acid (tretinoin), are exposed to cultured human fibroblasts, they produce a marked reduction of fibroblast proliferation and collagen synthesis. Our clinical study of keloids and hypertrophic scars demonstrates in vivo effects of retinoids that are consistent with the in vitro data. Retinoids have significant clinical activity on dermal tissue, and further in vitro and in vivo development and testing of retinoids may lead to significant therapeutic advances in the treatment of fibrotic diseases.

Topics: Cell Division; Cells, Cultured; Cicatrix; Collagen; Fibroblasts; Humans; In Vitro Techniques; Keloid; Retinoids; Skin; Tretinoin

Recent clinical observations have suggested that retinoids, which are in frequent use in dermatology, can affect the connective tissue metabolism in skin and other tissues. In this study, we examined the effects of several retinoids on the metabolism of collagen by human skin fibroblasts in culture. Incubation of cultured fibroblasts with all-trans-retinoic acid or 13-cis-retinoic acid, in 10(-5) M or higher concentrations, markedly reduced the procollagen production, as measured by synthesis of radioactive hydroxyproline. The effect was selective in that little, if any, inhibition was noted in the incorporation of [3H]leucine into the noncollagenous proteins, when the cells were incubated with the retinoids in 10(-5) M concentration. Similar reduction in procollagen production was noted with retinol and retinal, whereas an aromatic analogue of retinoic acid ethyl ester (RO-10-9359) resulted in a slight increase in procollagen production in these cultures. The reduction in procollagen production by all-trans-retinoic acid was accompanied by a similar reduction in pro alpha 2(I) of type I procollagen specific messenger RNA (mRNA), as detected by dot blot and Northern blot hybridizations. Hybridizations with human fibronectin and beta-actin specific DNA probes indicated that the levels of the corresponding mRNAs were not affected by the retinoids, further suggesting selectivity in the inhibition of procollagen gene expression. Further control experiments indicated that all-trans-retinoic acid, under the culture conditions employed, did not affect the posttranslational hydroxylation of prolyl residues, the mannosylation of newly synthesized procollagen, the specific radioactivity of the intracellular prolyltransfer RNA pool, or DNA replication. All-trans-retinoic acid also elicited a reduction in trypsin-activatable collagenase, but not in the activity of prolyl hydroxylase or an elastaselike neutral protease in the fibroblast cultures. Incubation of three fibroblast lines established from human keloids with all-trans-retinoic acid or 13-cis-retinoic acid also resulted in a marked reduction in procollagen production. The results, therefore, suggest that further development of retinoids might provide a novel means of modulating collagen gene expression in patients with various diseases affecting the connective tissues.

Topics: Cells, Cultured; Collagen; Endopeptidases; Fibroblasts; Gene Expression Regulation; Humans; Keloid; Mannose; Microbial Collagenase; Neprilysin; Procollagen; RNA, Messenger; Skin; Tretinoin

Topics: Female; Humans; Keloid; Male; Tretinoin

In a clinical trial twenty-eight intractable cases with scars were treated with daily applications of a 0.05% solution of retinoic acid. The results were evaluated objectively and subjectively. Slight to marked reduction of the size of these scars and decrease of such complaints as itching were noted in the majority of the cases. A favourable result was obtained according to the patients in 79%, and according to the opinion of the medical examiner in 77% of the patients.

Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Child, Preschool; Cicatrix; Female; Humans; Hypertrophy; Keloid; Male; Middle Aged; Tretinoin